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Publication : Targeting PKCθ Promotes Satellite Cell Self-Renewal.

First Author  Benedetti A Year  2020
Journal  Int J Mol Sci Volume  21
Issue  7 PubMed ID  32244482
Mgi Jnum  J:328161 Mgi Id  MGI:6835730
Doi  10.3390/ijms21072419 Citation  Benedetti A, et al. (2020) Targeting PKCtheta Promotes Satellite Cell Self-Renewal. Int J Mol Sci 21(7):2419
abstractText  Skeletal muscle regeneration following injury depends on the ability of satellite cells (SCs) to proliferate, self-renew, and eventually differentiate. The factors that regulate the process of self-renewal are poorly understood. In this study we examined the role of PKCtheta in SC self-renewal and differentiation. We show that PKCtheta is expressed in SCs, and its active form is localized to the chromosomes, centrosomes, and midbody during mitosis. Lack of PKCtheta promotes SC symmetric self-renewal division by regulating Pard3 polarity protein localization, without affecting the overall proliferation rate. Genetic ablation of PKCtheta or its pharmacological inhibition in vivo did not affect SC number in healthy muscle. By contrast, after induction of muscle injury, lack or inhibition of PKCtheta resulted in a significant expansion of the quiescent SC pool. Finally, we show that lack of PKCtheta does not alter the inflammatory milieu after acute injury in muscle, suggesting that the enhanced self-renewal ability of SCs in PKCtheta-/- mice is not due to an alteration in the inflammatory milieu. Together, these results suggest that PKCtheta plays an important role in SC self-renewal by stimulating their expansion through symmetric division, and it may represent a promising target to manipulate satellite cell self-renewal in pathological conditions.
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